Development and Characterization of Hygroscopicity-Controlled Sustain Release Formulation of Divalproex Sodium.

Abstract

Objectives: Divalproex sodium (DS), being a hygroscopic drug, requires low humidity during product manufacturing. This study aims to develop a hygroscopicity controlled sustained release formulation of DS that can be manufactured in relatively high humid conditions in facilities lacking dehumidifiers.

Materials and methods: This study focuses on the role of polyethylene glycol (PEG-8000) and hydroxypropyl methylcellulose (HPMC K100M) as polymers of choice to control hygroscopicity and retard release of DS using solid dispersion technique. In this study, homogeneous solid dispersions containing various ratios of PEG-8000, HPMC K100M, and DS were obtained via melt granulation technique. Fifteen different solid dispersions were prepared based on Box-Behnken experimental design created in MiniTab software. The obtained solid dispersions were separately broken down into granules and their hygroscopic properties were determined via moisture uptake studies. Granular solid dispersions were then compressed into tablets and their sustained release dissolution profiles were studied as per the United States Pharmacopoeia (USP) monograph of DS extended-release tablets. Dissolution profiles of all fifteen formulations were then analyzed in Box-Behnken experimental design under MiniTab software to determine an optimized formulation having low hygroscopic properties as well as required multipoint drug release as per USP monograph. The final optimized formulation was prepared and subjected to moisture uptake study to determine its hygroscopicity, dissolution study to determine drug release kinetics and fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) analysis to determine molecular interactions between drug and polymers.

Result: Optimized final formulation yielded granular solid dispersion with 28% less hygroscopicity compared to DS and tablets with an excellent release profile in accordance with USP monograph. FTIR and DSC analysis did not show any significant interaction between DS and components of the solid dispersion.

Conclusion: Optimized formulation from this study can be used to manufacture divalproex extended-release tablets inside facilities lacking dehumidifiers.